Biological effects of inhibitors of S-adenosylhomocysteine hydrolase.


:S-Adenosylhomocysteine (AdoHcy), formed after the donation of the methyl group of S-adenosylmethionine to a methyl acceptor, is hydrolyzed to adenosine and homocysteine by AdoHcy hydrolase physiologically. The administration of the inhibitors of AdoHcy hydrolase to cells or animals normally results in an accumulation of cellular AdoHcy higher than those found in controls, which is often accompanied by a simultaneous rise in S-adenosylmethionine because of the feedback inhibition by AdoHcy on most methylation reactions. AdoHcy hydrolase has become a tantalizing pharmacological target for inhibition since its blockade can affect cellular methylation of phospholipids, proteins, small molecules, DNA, and RNA. Indeed, all of these different methylation reactions have been found to be inhibitable by the nucleoside inhibitors/substrates of AdoHcy hydrolase. Among the interesting effects are the activation of genes, induction of cellular differentiation, increased expression of transcription factors, and sometimes the repression of genes. Furthermore, some of the nucleosides show remarkable antiviral activities in vitro and in vivo. However, the mode of action of the inhibitors appears complex. Although the inhibition of methylation might account for some of the biological effects, the ability of some of the nucleoside inhibitors to undergo metabolic phosphorylation to nucleotides may account for part of their biological activities. The defining mode of action responsible for their biological effects still awaits biochemical elaboration, especially regarding their antiviral effects, induction of genes, or cellular differentiation.


Pharmacol Ther


Chiang PK




Has Abstract


1998-02-01 00:00:00














  • Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches.

    abstract::The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called "cardiovascular risk factors" are associated with endothelial dys...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Tousoulis D,Simopoulou C,Papageorgiou N,Oikonomou E,Hatzis G,Siasos G,Tsiamis E,Stefanadis C

    更新日期:2014-12-01 00:00:00

  • Use of glucocorticoids in the critical care setting: Science and clinical evidence.

    abstract::Glucocorticoids (GC) in all its various forms and formulations are likely one of the most commonly used pharmacologic agents in medicine. Their use can be profoundly therapeutic but are also associated with a myriad of acute and chronic side effects. It is fairly well-accepted in the medical community that GC can be l...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Chan ED,Chan MM,Chan MM,Marik PE

    更新日期:2020-02-01 00:00:00

  • Current investigations on clinical pharmacology and therapeutics of Glucose-6-phosphate dehydrogenase deficiency.

    abstract::Glucose-6-phospate dehydrogenase (G6PD) deficiency is estimated to affect more than 400 million people world-wide. This X-linked genetic deficiency puts stress on red blood cells (RBC), which may be further augmented under certain pathophysiological conditions and drug treatments. These conditions can cause hemolytic ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Ryan K,Tekwani BL

    更新日期:2020-12-14 00:00:00

  • The structure and mechanism of bacterial type I signal peptidases. A novel antibiotic target.

    abstract::Type I signal peptidases are essential membrane-bound serine proteases that function to cleave the amino-terminal signal peptide extension from proteins that are translocated across biological membranes. The bacterial signal peptidases are unique serine proteases that utilize a Ser/Lys catalytic dyad mechanism in plac...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章


    authors: Paetzel M,Dalbey RE,Strynadka NC

    更新日期:2000-07-01 00:00:00

  • Therapeutic targets in pulmonary arterial hypertension.

    abstract::Pulmonary arterial hypertension is a progressive, fatal disease. Current treatments including prostanoids, endothelin-1 (ET-1) antagonists, and phosphodiesterase (PDE) inhibitors, have sought to address the pulmonary vascular endothelial dysfunction and vasoconstriction associated with the condition. These treatments ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Rhodes CJ,Davidson A,Gibbs JS,Wharton J,Wilkins MR

    更新日期:2009-01-01 00:00:00

  • PICK1: a multi-talented modulator of AMPA receptor trafficking.

    abstract::AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor trafficking is a fundamental mechanism for regulating synaptic strength, and hence may underlie cellular processes involved in learning and memory. PICK1 (protein interacting with C-kinase) is a PDZ and BAR domain-containing protein that has rece...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Hanley JG

    更新日期:2008-04-01 00:00:00

  • Antimicrobial peptides, nanotechnology, and natural metabolites as novel approaches for cancer treatment.

    abstract::Despite the advances in tumor identification and treatment, cancer remains the primary driver of death around the world. Also, regular treatments for the disease are incapable of targeting particular cancer types at different stages since they are not specifically focused on harmful cells since they influence both sol...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Leite ML,da Cunha NB,Costa FF

    更新日期:2018-03-01 00:00:00

  • Targeting cell cycle regulation in cancer therapy.

    abstract::Cell proliferation is an essential mechanism for growth, development and regeneration of eukaryotic organisms; however, it is also the cause of one of the most devastating diseases of our era: cancer. Given the relevance of the processes in which cell proliferation is involved, its regulation is of paramount importanc...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Diaz-Moralli S,Tarrado-Castellarnau M,Miranda A,Cascante M

    更新日期:2013-05-01 00:00:00

  • Mechanisms of aspirin resistance.

    abstract::Aspirin is integral to the secondary prevention of cardiovascular disease and acts to impair the development of platelet-mediated atherothromboembolic events by irreversible inhibition of platelet cyclooxygenase-1 (COX-1). Inhibition of this enzyme prevents the synthesis of the potent pro-aggregatory prostanoid thromb...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Floyd CN,Ferro A

    更新日期:2014-01-01 00:00:00

  • A role for 5-HT in the action of antidepressant drugs.

    abstract::Administration of antidepressant drugs to rodents appears to decrease 5-HT2 receptor function while transmission through postsynaptic 5-HT1 receptor synapses may be enhanced. Antidepressant drugs also alter 5-HT mechanisms in humans; some of these changes are congruent with effects noted in animal studies. Thus certai...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Cowen PJ

    更新日期:1990-01-01 00:00:00

  • Synaptic plasticity and phosphorylation.

    abstract::A number of neuronal functions, including synaptic plasticity, depend on proper regulation of synaptic proteins, many of which can be rapidly regulated by phosphorylation. Neuronal activity controls the function of these synaptic proteins by exquisitely regulating the balance of various protein kinase and protein phos...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Lee HK

    更新日期:2006-12-01 00:00:00

  • The canine model with chronic, complete atrio-ventricular block.

    abstract::Proarrhythmic susceptibility to drug-induced Torsades de Pointes is restricted to individuals with a predisposed phenotype characterized by a reduced repolarization reserve. Additional factors are often involved in a further impairment of repolarization, possibly culminating with dangerous ventricular polymorphic tach...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Oros A,Beekman JD,Vos MA

    更新日期:2008-08-01 00:00:00

  • Potential role of female sex hormones in the pathophysiology of migraine.

    abstract::Clinical evidence indicates that female sex steroids may contribute to the high prevalence of migraine in women, as well as changes in the frequency or severity of migraine attacks that are in tandem with various reproductive milestones in women's life. While female sex steroids do not seem to be involved in the patho...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Gupta S,Mehrotra S,Villalón CM,Perusquía M,Saxena PR,MaassenVanDenBrink A

    更新日期:2007-02-01 00:00:00

  • Protein kinase inhibitors and antibiotic resistance.

    abstract::While antibiotics revolutionized the treatment of infectious disease in the 20th century, bacterial resistance now threatens to render many of them ineffective. Aminoglycosides are a class of clinically important antibiotics used in the treatment of infections caused by Gram-positive and -negative organisms. They are ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Burk DL,Berghuis AM

    更新日期:2002-02-01 00:00:00

  • PARP inhibition in the ovarian cancer patient: Current approvals and future directions.

    abstract::Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as bio...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Kurnit KC,Avila M,Hinchcliff EM,Coleman RL,Westin SN

    更新日期:2020-09-01 00:00:00

  • Cancer immunotherapy with immunoadjuvants, nanoparticles, and checkpoint inhibitors: Recent progress and challenges in treatment and tracking response to immunotherapy.

    abstract::Chemotherapy, surgery, and radiation are accepted as the preferred treatment modalities against cancer, but in recent years the use of immunotherapeutic approaches has gained prominence as the fourth treatment modality in cancer patients. In this approach, a patient's innate and adaptive immune systems are activated t...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Gorbet MJ,Ranjan A

    更新日期:2020-03-01 00:00:00

  • Smooth muscle of the bladder in the normal and the diseased state: pathophysiology, diagnosis and treatment.

    abstract::The smooth muscle of the normal bladder wall must have some specific properties. It must be very compliant and able to reorganise itself during filling and emptying to accommodate the change in volume without generating any intravesical pressure, but whilst maintaining the normal shape of the bladder. It must be capab...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Turner WH,Brading AF

    更新日期:1997-08-01 00:00:00

  • Unfaithful neurotransmitter transporters: focus on serotonin uptake and implications for antidepressant efficacy.

    abstract::Biogenic amine transporters for serotonin, norepinephrine and dopamine (SERT, NET and DAT respectively), are the key players terminating transmission of these amines in the central nervous system by their high-affinity uptake. They are also major targets for many antidepressant drugs. Interestingly however, drugs targ...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Daws LC

    更新日期:2009-01-01 00:00:00

  • Metabolic zonation of the liver: regulation and implications for liver function.

    abstract::Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the va...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Gebhardt R

    更新日期:1992-01-01 00:00:00

  • Environmental neurotoxic chemicals-induced ubiquitin proteasome system dysfunction in the pathogenesis and progression of Parkinson's disease.

    abstract::Proteolytic degradation of unwanted proteins by the ubiquitin-proteasome system (UPS) is critical for normal maintenance of various cellular functions. Parkinson's disease (PD), one of the most prevalent neurodegenerative disorders, is characterized by prominent and irreversible nigral dopaminergic neuronal loss and i...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Sun F,Kanthasamy A,Anantharam V,Kanthasamy AG

    更新日期:2007-06-01 00:00:00

  • Nutraceuticals and osteoarthritis pain.

    abstract::Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current ther...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Wang A,Leong DJ,Cardoso L,Sun HB

    更新日期:2018-07-01 00:00:00

  • Gender disparity in cardiac electrophysiology: implications for cardiac safety pharmacology.

    abstract:BACKGROUND:Gender differences in cardiac electrophysiology were reported for the first time almost a century ago. The importance for safety pharmacology became significant when modern medicine came into use and women appeared to be more susceptible to drug-induced Torsade de Pointes (TdP). To unravel the underlying mec...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Jonsson MK,Vos MA,Duker G,Demolombe S,van Veen TA

    更新日期:2010-07-01 00:00:00

  • Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing.

    abstract::Artemisinins are a unique class of antimalarial drugs with significant potential for drug repurposing for a wide range of diseases including cancer. Cancer is a leading cause of death globally and the majority of cancer related deaths occur in Low and Middle Income Countries (LMICs) where conventional treatment option...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Augustin Y,Staines HM,Krishna S

    更新日期:2020-12-01 00:00:00

  • Neuropharmacology of 5-hydroxytryptamine1B/D receptor ligands.

    abstract::In spite of a lack of compounds acting selectively at the 5-hydroxytryptamine (5-HT)1B and 5-HT1D receptor subtypes, by cross-relating the available data, this review attempts to tentatively assign behavioural and other in vivo correlates of these receptor subtypes. In addition, a summary of data from microdialysis st...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Chopin P,Moret C,Briley M

    更新日期:1994-01-01 00:00:00

  • Transcranial magnetic brain stimulation: therapeutic promises and scientific gaps.

    abstract::Since its commercial advent in 1985, transcranial magnetic stimulation (TMS), a technique for stimulating neurons in the cerebral cortex through the scalp, safely and with minimal discomfort, has captured the imaginations of scientists, clinicians and lay observers. Initially a laboratory tool for neurophysiologists s...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Wassermann EM,Zimmermann T

    更新日期:2012-01-01 00:00:00

  • Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information.

    abstract::The aim of the present paper was to present an overview of the current status of the methods used to predict the magnitude of pharmacokinetic drug-drug interactions (DDIs) which are caused by apparent changes in cytochrome P450 (CYP) activity with an emphasis on a method using in vivo information. In addition, more th...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Hisaka A,Ohno Y,Yamamoto T,Suzuki H

    更新日期:2010-02-01 00:00:00

  • Use of biologics to treat acute exacerbations and manage disease in asthma, COPD and IPF.

    abstract::A common feature of chronic respiratory disease is the progressive decline in lung function. The decline can be indolent, or it can be accelerated by acute exacerbations, whereby the patient experiences a pronounced worsening of disease symptoms. Moreover, acute exacerbations may also be a marker of insufficient disea...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Murray LA,Grainge C,Wark PA,Knight DA

    更新日期:2017-01-01 00:00:00

  • Drug uptake transporters in antiretroviral therapy.

    abstract::Current treatment of human immunodeficiency virus-1 (HIV-1) infection is effective, although it does not permanently suppress viral replication in all patients. Viral persistence, drug toxicity, and antiretroviral resistance are challenging barriers to successful treatment of HIV-1 infection. It has become increasingl...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Minuesa G,Huber-Ruano I,Pastor-Anglada M,Koepsell H,Clotet B,Martinez-Picado J

    更新日期:2011-12-01 00:00:00

  • VMAT2 inhibitors for the treatment of hyperkinetic movement disorders.

    abstract::Hyperkinetic movement disorders comprise a variety of conditions characterized by involuntary movements, which include but are not limited to tardive dyskinesia, chorea associated with Huntington's Disease, and tic disorders. The class of medications that have been used to treat these conditions includes Vesicular Mon...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Koch J,Shi WX,Dashtipour K

    更新日期:2020-08-01 00:00:00

  • Small molecules affecting transcription in Friedreich ataxia.

    abstract::This review concerns the development of small molecule therapeutics for the inherited neurodegenerative disease Friedreich ataxia (FRDA). FRDA is caused by transcriptional repression of the nuclear FXN gene, encoding the essential mitochondrial protein frataxin and accompanying loss of frataxin protein. Frataxin insuf...

    journal_title:Pharmacology & therapeutics

    pub_type: 杂志文章,评审


    authors: Gottesfeld JM

    更新日期:2007-11-01 00:00:00